Association of transforming growth factor-β1 gene C-509T and T869C polymorphisms with atherosclerotic cerebral infarction in the Chinese: a case-control study

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. There is scant information on the relation between variations within the TGF-β1 gene polymorphisms and risks of ischemic cerebrovascular diseases. Therefore, this case-controlled study was carried out to investigate the possible association of the TGF-β1 gene C-509T and T869C polymorphisms, and their combined genotypes with the risk of atherosclerotic cerebral infarction (CI) in the Chinese population.</p> <p>Results</p> <p>We recruited 164 CI patients and 167 healthy control subjects who were frequency-matched for age and gender. The frequencies of the -509TT genotype and T allele gene were significantly higher in the CI group (<it>P </it>= 0.007, <it>P </it>= 0.006). The frequencies of +869CC genotype and C allele were higher in the CI group (<it>P </it>= 0.002, <it>P </it>= 0.004). In the CI group, the individuals with -509TT genotype had a significantly higher level of plasma triglyceride (TG) (<it>P </it>= 0.017). +869CC genotype correlated significantly with higher level of plasma low density lipoprotein cholesterol (LDL-c) in the CI group (<it>P </it>= 0.015). With haplotype analysis, the frequency of the -509T/+869C combined genotype was significantly higher in the CI group than in controls (<it>P </it>< 0.001).</p> <p>Conclusions</p> <p>Our study suggests that C-509T and T869C gene polymorphisms in TGF-β1 may be a critical risk factor of genetic susceptibility to CI in the Chinese population.</p

Dynamic Evolution and Correlation between Metabolites and Microorganisms during Manufacturing Process and Storage of Fu Brick Tea

Fu brick tea (FBT) is one of the major brands of dark tea. Microbial fermentation is considered the key step in the development of the special characteristics of FBT. The systemic corelationship of the microbiome and metabolomics during manufacture of Fu brick tea is not fully understood. In this study, we comprehensively explored the microbiome and metabolite dynamic evolution during the FBT manufacturing processes, and revealed decisive factors for the quality and safety of FBT based on the grouped methods of metabolomics combined with biochemical measurements, microbiome sequencing combined with quantitative polymerase chain reaction (PCR), and multiplex analysis. Both the microbiome and quantitative PCR showed that fungi displayed concentrated distribution characteristics in the primary dark tea samples, while bacterial richness increased during the flowering processes and ripening period. All microorganism species, as well as dominant fungi and bacteria, were identified in the distinct processes periods. A total of 178 metabolites were identified, and 34 of them were characterized as critical metabolites responsible for metabolic changes caused by the corresponding processes. Metabolic analysis showed that most metabolites were decreased during the FBT manufacturing processes, with the exception of gallic acid. Multivariate analysis verified that the critical metabolites were correlated with specific dominant microbial species. All the top fungal species except unclassified_g_ Aspergillus showed positive correlations with six critical metabolites (L-The, epigallocatechin (EGC), Gln, tea polyphenol (TP), tea polysaccharides (TPs) and caffeine). Five of the top bacteria species (Cronobacter, Klebsiella, Pantoea, Pluralibacter, and unclassified_ f_Entero-bacteriaceae) showed positive correlations with epigallocatechins and tea polyphenols, while the other 11 top bacterial species correlated negatively with all the critical metabolites. The content of amino acids, tea polyphenols, tea polysaccharides, and flavonoids was reduced during microbial fermentation. In conclusion, our results reveal that microbial composition is the critical factor in changing the metabolic profile of FBT. This discovery provides a theoretical basis for improving the quality of FBT and enhancing its safety

The prognostic value of deep earlobe creases in patients with acute ischemic stroke

Background and purposeData on earlobe crease (ELC) among patients with acute ischemic stroke (AIS) are limited. Here, we determined the frequency and characteristics of ELC and the prognostic effect of ELC among AIS patients.MethodsA total of 936 patients with acute AIS were enrolled during the period between December 2018 and December 2019. The patients were divided into those without and with ELC, unilateral and bilateral ELC, and shallow and deep ELC, according to the photographs taken of the bilateral ears. Logistic regression models were used to estimate the effect of ELC, bilateral ELC, and deep ELC on poor functional outcomes at 90 days (a modified Rankin Scale score ≥2) in AIS patients.ResultsAmong the 936 AIS patients, there were 746 (79.7%) patients with ELC. Among patients with ELC, there were 156 (20.9%) patients with unilateral ELC and 590 (79.1%) with bilateral ELC and 476 (63.8%) patients with shallow ELC and 270 (36.2%) with deep ELC. After adjusting for age, sex, baseline NIHSS score, and other potential covariates, patients with deep ELC were associated with a 1.87-fold [odds ratio (OR) 1.87; 95% confidence interval (CI), 1.13–3.09] and 1.63-fold (OR 1.63; 95%CI, 1.14–2.34) increase in the risk of poor functional outcome at 90 days in comparison with those without ELC or shallow ELC.ConclusionELC was a common phenomenon, and eight out of ten AIS patients had ELC. Most patients had bilateral ELC, and more than one-third had deep ELC. Deep ELC was independently associated with an increased risk of poor functional outcome at 90 days

BASP1 is a prognostic biomarker associated with immunotherapeutic response in head and neck squamous cell carcinoma

BackgroundsImmunotherapy is effective in a subset of head and neck squamous cell carcinoma (HNSCC). However, the unfavorable response rate and inadequate biomarkers for stratifying patients have primarily limited its clinical application. Considering transcriptional factors (TFs) play essential roles in regulating immune activity during HNSCC progression, we comprehensively analyzed the expression alterations of TFs and their prognostic values.MethodsGene expression datasets and clinical information of HNSCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository. Then, Brain abundant membrane attached signal protein 1 (BASP1) was screened out of differentially expressed TFs by univariate and multivariate survival analysis. Tumor immune dysfunction and exclusion (TIDE) was applied to analyze the response to immunotherapy of BASP1high/low patients. Meanwhile, GO, KEGG and GSEA analyses were used to enrich the pathways between the BASP1high and BASP1low groups. Single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, EPIC and quanTiseq algorithms were applied to explore immune infiltrations. Also, immune cycle analysis was conducted by ssGSEA. Additionally, lipid peroxidation, glutathione and reactive oxygen species were performed to detect the ferroptosis alternations.ResultsBASP1 was upregulated and associated with poor survival in HNSCC patients. BASP1high patients exhibited better response rates to anti-PD-1 immunotherapy and higher expressions of immune checkpoint inhibitors. GO, KEGG and GSEA analyses indicated that the expression of BASP1 was related to several immune-related pathways and immunogenic ferroptosis signature. The infiltration of activated CD8+ T cells was authenticated to be decreased in BASP1high patients. Furthermore, BASP1 was identified to be positively correlated with T cell dysfunction and immune escape. Moreover, silencing BASP1 triggered ferroptosis in HNSCC cells, representing as increased LDH, lipid peroxidation and ROS levels, and reduced glutathione synthesisConclusionsWe demonstrated that BASP1 suppressed immunogenic ferroptosis to induce immunosuppressive tumor microenvironment. BASP1 plays a critical role in immune response, and might be a promising classifier for selecting HNSCC patients who benefit from current immunotherapy

Distinguishing two-component anomalous Hall effect from topological Hall effect in magnetic topological insulator MnBi2Te4

In transport, the topological Hall effect (THE) is widely interpreted as a sign of chiral spin textures, like magnetic skyrmions. However, the co-existence of two anomalous Hall effects (AHE) could give rise to similar non-monotonic features or "humps", making it difficult to distinguish between the two. Here we demonstrate that the "artifact" two-component anomalous Hall effect can be clearly distinguished from the genuine topological Hall effect by three methods: 1. Minor loops 2. Temperature dependence 3. Gate dependence. One of the minor loops is a single loop that cannot fit into the full AHE loop under the assumption of AHE+THE. In addition, by increasing the temperature or tuning the gate bias, the emergence of humps is accompanied by a polarity change of the AHE. Using these three methods, one can find the humps are from another AHE loop with a different polarity. Our material is a magnetic topological insulator MnBi2Te4 grown by molecular beam epitaxy, where the presence of the secondary phase MnTe2 on the surface contributes to the extra positive AHE component. Our work may help future researchers to exercise cautions and use these three methods to examine carefully in order to ascertain genuine topological Hall effect

Topology hierarchy of transition metal dichalcogenides built from quantum spin Hall layers

The evolution of the physical properties of two-dimensional material from monolayer limit to the bulk reveals unique consequences from dimension confinement and provides a distinct tuning knob for applications. Monolayer 1T'-phase transition metal dichalcogenides (1T'-TMDs) with ubiquitous quantum spin Hall (QSH) states are ideal two-dimensional building blocks of various three-dimensional topological phases. However, the stacking geometry was previously limited to the bulk 1T'-WTe2 type. Here, we introduce the novel 2M-TMDs consisting of translationally stacked 1T'-monolayers as promising material platforms with tunable inverted bandgaps and interlayer coupling. By performing advanced polarization-dependent angle-resolved photoemission spectroscopy as well as first-principles calculations on the electronic structure of 2M-TMDs, we revealed a topology hierarchy: 2M-WSe2, MoS2, and MoSe2 are weak topological insulators (WTIs), whereas 2M-WS2 is a strong topological insulator (STI). Further demonstration of topological phase transitions by tunning interlayer distance indicates that band inversion amplitude and interlayer coupling jointly determine different topological states in 2M-TMDs. We propose that 2M-TMDs are parent compounds of various exotic phases including topological superconductors and promise great application potentials in quantum electronics due to their flexibility in patterning with two-dimensional materials